Salonurmi Tuire, Parikka Mataleena, Kontusaari Sirpa, Pirilä Emma, Munaut Carine, Salo Tuula, Tryggvason Karl
Biocenter Oulu, Department of Biochemistry, University of Oulu, Oulu, Finland.
Cell Tissue Res. 2004 Jan;315(1):27-37. doi: 10.1007/s00441-003-0814-1. Epub 2003 Oct 21.
We have generated transgenic mice harboring the murine matrix metalloproteinase 9 (MMP-9) promoter cloned in front of human TIMP-1 cDNA. The transgenic mice were viable and fertile and exhibited normal growth and general development. During wound healing the mice were shown to express human TIMP-1 in keratinocytes that normally express MMP-9. However, the healing of skin wounds was significantly retarded with slow migration of keratinocytes over the wound in transgenic mice. In situ zymography carried out on wound tissues revealed total blockage of gelatinolytic activity (i.e., MMP-9 and MMP-2). The results confirm studies with MMP-9 knockout mice showing that MMP-9 is not essential for general development, but they also demonstrate an important role of keratinocyte MMP-9, as well that of other keratinocyte MMPs that are inhibited by TIMP-1, in wound healing. The transgenic mice generated in this study provide a model for the role of MMPs in MMP-9-producing cells in other challenging situations such as bone fracture recovery and cancer invasion.
我们构建了转基因小鼠，其携带克隆在人组织金属蛋白酶抑制因子-1（TIMP-1）cDNA上游的小鼠基质金属蛋白酶9（MMP-9）启动子。这些转基因小鼠可存活且可育，生长和整体发育正常。在伤口愈合过程中，这些小鼠被证明在正常表达MMP-9的角质形成细胞中表达人TIMP-1。然而，转基因小鼠的皮肤伤口愈合明显延迟，角质形成细胞在伤口上的迁移缓慢。对伤口组织进行的原位酶谱分析显示明胶酶活性（即MMP-9和MMP-2）完全被阻断。这些结果证实了对MMP-9基因敲除小鼠的研究，表明MMP-9对整体发育并非必不可少，但它们也证明了角质形成细胞MMP-9以及其他被TIMP-1抑制的角质形成细胞MMPs在伤口愈合中的重要作用。本研究中产生的转基因小鼠为MMPs在诸如骨折恢复和癌症侵袭等其他具有挑战性的情况下在产生MMP-9的细胞中的作用提供了一个模型。
